Pelvic fracture-related hypotension: A review of contemporary adjuncts for hemorrhage control.
Major pelvic hemorrhage remains a considerable challenge of modern trauma care associated with mortality in over a third of patients. Efforts to improve outcomes demand continued research into the optimal employment of both traditional and newer hemostatic adjuncts across the full spectrum of emergent care environments. The purpose of this review is to provide a concise description of the rationale for and effective use of currently available adjuncts for the control of pelvic hemorrhage. In addition, the challenges of defining the optimal order and algorithm for employment of these adjuncts will be outlined. Review, level IV.


A role for adaptor protein-3 complex in the organization of the endocytic pathway in Dictyostelium.
Dictyostelium discoideum cells continuously internalize extracellular material, which accumulates in well-characterized endocytic vacuoles. In this study, we describe a new endocytic compartment identified by the presence of a specific marker, the p25 protein. This compartment presents features reminiscent of mammalian recycling endosomes: it is localized in the pericentrosomal region but distinct from the Golgi apparatus. It specifically contains surface proteins that are continuously endocytosed but rapidly recycled to the cell surface and thus absent from maturing endocytic compartments. We evaluated the importance of each clathrin-associated adaptor complex in establishing a compartmentalized endocytic system by studying the phenotype of the corresponding mutants. In knockout cells for mu3, a subunit of the AP-3 clathrin-associated complex, membrane proteins normally restricted to p25-positive endosomes were mislocalized to late endocytic compartments. Our results suggest that AP-3 plays an essential role in the compartmentalization of the endocytic pathway in Dictyostelium.


Ipsilesional attentional-approach neglect or crossover effect.
Patients with ipsilateral neglect (IN) bisect lines toward contralesional space. It has been posited that IN might be induced by an attempt at compensation, as part of the crossover effect, where patients with an ipsilesional bias when bisecting long lines, cross over and develop a contralesional bias on short lines or as a release of an approach (grasp) behavior that might be attentional or intentional. To test these alternative hypotheses we had a patient with IN from a right medial frontal lesion bisect lines that contained no cue, a left-sided cue, a right-sided cue, and bilateral cues. If this patient had ipsilateral neglect (IN) because of a crossover effect or compensation, right-sided cues should have influenced bisection more than left-sided cues. We, however, found that only left-sided cues induced a significant change (left-sided deviation) providing support for the attentional-approach (grasp) hypothesis. Further support of this contralesional attentional grasp hypothesis comes from the observation that this patient also had ipsilesional extinction to simultaneous stimuli.


Radioisotope dilution determination of vitamin B12 in dietary supplements.
A rapid and sensitive method for the determination of vitamin B12 in dietary supplements has been developed using a commercially available radioisotope dilution (RID) kit. The vitamin B12 was isolated by enzymatic extraction.


Travel medicine: what's involved? When to refer?
To define the practice of travel medicine, provide the basics of a comprehensive pretravel consultation for international travelers, and assist in identifying patients who might require referral to travel medicine professionals. Guidelines and recommendations on travel medicine and travel-related illnesses by national and international travel health authorities were reviewed. MEDLINE and EMBASE searches for related literature were also performed. Travel medicine is a highly dynamic specialty that focuses on pretravel preventive care. A comprehensive risk assessment for each individual traveler is essential in order to accurately evaluate traveler-, itinerary-, and destination-specific risks, and to advise on the most appropriate risk management interventions to promote health and prevent adverse health outcomes during travel. Vaccinations might also be required and should be personalized according to the individual traveler's immunization history, travel itinerary, and the amount of time available before departure. A traveler's health and safety depends on a practitioner's level of expertise in providing pretravel counseling and vaccinations, if required. Those who advise travelers are encouraged to be aware of the extent of this responsibility and to refer all high-risk travelers to travel medicine professionals whenever possible.


[The role of postoperative radiotherapy in the treatment of hypernephroid carcinoma].
The following results can be derived from the clinical and radiobiological literature as well as from the authors's own experiences with 91 patients analyzed retrospectively and evaluated with respect to their risk factors. 1. A postoperative irradiation is very probably sensible in patients with tumor perforation through the renal capsule (T3/T4) and with venous or lymph node manifestations. 2. The operation method is essential, above all the transabdominal technique and the quality of lymph dissection. 3. Prospective studies are necessary in order to clear up the role of radiotherapy in patients with lymph node manifestations and the other two risk factors mentioned in item 1. 4. Further studies on the tumor biology of the hypernephroid carcinoma are necessary in order to gain prognostic criteria allowing a pretherapeutic sensitivity recognition. 5. The effect of a supplementary radiotherapy can be only that of local recurrence prevention in case of a locally advanced tumor and the absence of demonstrable remote metastases. This seems justified, because the local recurrence rate in our own patients was only 3.3%.


A Multi-Institutional Assessment of Factors Influencing Locomotion and Pacing in Captive Okapis (Okapia johnstoni).
The okapi (Okapia johnstoni), native to the Democratic Republic of Congo, is a large, solitary, and diurnal forest-dwelling ungulate highly sensitive to captive conditions. The captive population demonstrates persistent health problems, reproductive abnormalities, and several potentially abnormal repetitive behaviors. This study reports on locomotion and pacing in adult male and female okapis. Commonly, data on repetitive behavior have been derived from surveys. Although insightful, the results are often highly generalized and provide little information about the true preponderance and nature of such behavior in a population. In this study, direct observations determining how often and when a behavior of interest occurs are paired with information on factors (intrinsic and extrinsic) that can impact a nonhuman animal's propensity to perform repetitive behavior. More than half of the North American okapi population comprised the study population. Each animal was studied for 2 summer and winter seasons. Factors predictive of pacing in both males and females included 3 housing and habitat factors and 4 management factors. Patterns of locomotion and the rate and pattern of pacing in males when compared with females suggested different mechanisms may be driving these behaviors in the different sexes and that a sex-specific management strategy would benefit this species.


Lab-On-a-Chip for carbon nanotubes based immunoassay detection of Staphylococcal Enterotoxin B (SEB).
We describe a new eight channel Lab-On-a-Chip (LOC) for a Carbon Nanotube (CNT) based immunoassay with optical detection of Staphylococcal Enterotoxin B (SEB) for food safety applications. In this work, we combined four biosensing elements: (1) CNT technology for primary antibody immobilization, (2) Enhanced Chemiluminescence (ECL) for light signal generation, (3) a cooled charge-coupled device (CCD) for detection and (4) polymer lamination technology for developing a point of care immunological assay for SEB detection. Our concept for developing versatile LOCs, which can be used for many different applications, is to use a modular design with interchangeable recognition elements (e.g. various antibodies) to determine the specificity. Polymer lamination technology was used for the fabrication of a six layer, syringe operated LOC capable of analyzing eight samples simultaneously. An anti-SEB antibody-nanotube mixture was immobilized onto a polycarbonate strip, to serve as an interchangeable ligand surface that was then bonded onto the LOC. SEB samples are loaded into the device and detected by an ELISA assay using Horse Radish Peroxidase (HRP) conjugated anti-SEB IgG as a secondary antibody and ECL, with detection by a previously described portable cooled CCD detector. Eight samples of SEB in buffer or soy milk were assayed simultaneously with a limit of detection of 0.1 ng mL(-1). CNT immobilization of the antibody increased the sensitivity of detection six fold. Use of a simple interchangeable immunological surface allows this LOC to be adapted to any immunoassay by simply replacing the ligand surface. A syringe was used to move fluids for this assay so no power is needed to operate the device. Our versatile portable point-of-care CCD detector combined with the LOC immunoassay method described here can be used to reduce the exposure of users to toxins and other biohazards when working outside the lab, as well as to simplify and increase sensitivity for many other types of immunological diagnostics and detection assays.


The relationship between metabolic syndrome and increased risk of Barrett's esophagus: an updated systematic review and meta-analysis.
The relationship between metabolic syndrome (MetS) and Barrett's esophagus (BE) is still a challenging issue, and inconsistent results have been reported in different studies. Therefore, this study was conducted to determine the relationship between MetS and BE. In this study, we followed the MOOSE protocol and results were reported according to the PRISMA guidelines. All study steps were performed independently by two authors. If necessary, the dispute was resolved by consultation with a third author. The search strategy is designed to find published studies. Comprehensive search was done in the following databases until July 2019: Cochrane Library, PubMed/Medline, Web of Science, Science Direct, EMBASE, Scopus, CINAHL, EBSCO, and Google Scholar search engine. All analyses were performed using Comprehensive Meta-Analysis Software Ver.2, while p-value lower than 0.05 was considered significant. In 14 studies with a sample size of 108,416, MetS significantly increased the risk of BE (OR = 1.354; 95% CI: 1.145-1.600; P < 0.001; Heterogeneity: I2 = 81.95%; P < 0.001). Sensitivity analysis by omitting one study showed that overall estimates are still robust. Subgroup analysis was significant for continent (P < 0.001) and MetS diagnostic criteria (P = 0.043), but was not significant for variables of study type (P = 0.899), study setting (P = 0.115), control groups (P = 0.671) and quality of studies (P = 0.603). The Begg (P = 0.912) and Egger's (P = 0.094) tests were not significant; therefore, the publication bias did not play a role in the results. MetS increases the risk of BE compared to control groups. The results of this study can help health practitioners by identifying a treatable risk factor for the most important risk factor for esophageal carcinoma (ie, BE). Future studies should examine whether treatment for MetS reduces the risk of BE.


Linkage disequilibrium of polymorphic sites in the G6PD gene in African populations and the origin of G6PD A-.
So far, four polymorphic sites are known to exist in the glucose 6-phosphate dehydrogenase (G6PD) gene of people of African origin: the mutation in G6PD A (which creates a FokI restriction enzyme site); the additional mutation in G6PD A- (which creates an NlaIII site); and two restriction fragment length polymorphisms (PvuII and PstI). We have investigated the status of these four sites in 78 men of African descent and found them to exist in linkage disequilibrium--only five of the ten haplotypes expected at least twice under a random assortment regimen were observed. The mutation of G6PD A- is found only in the presence of the PvuII and PstI sites and we therefore suggest that it has arisen only once. We propose a likely sequence for the evolution of these different mutations in the G6PD gene.


STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors.
Spontaneous T cell responses against tumors occur frequently and have prognostic value in patients. The mechanism of innate immune sensing of immunogenic tumors leading to adaptive T cell responses remains undefined, although type I interferons (IFNs) are implicated in this process. We found that spontaneous CD8(+) T cell priming against tumors was defective in mice lacking stimulator of interferon genes complex (STING), but not other innate signaling pathways, suggesting involvement of a cytosolic DNA sensing pathway. In vitro, IFN-? production and dendritic cell activation were triggered by tumor-cell-derived DNA, via cyclic-GMP-AMP synthase (cGAS), STING, and interferon regulatory factor 3 (IRF3). In the tumor microenvironment in vivo, tumor cell DNA was detected within host antigen-presenting cells, which correlated with STING pathway activation and IFN-? production. Our results demonstrate that a major mechanism for innate immune sensing of cancer occurs via the host STING pathway, with major implications for cancer immunotherapy.


Health law in Europe: from the present to the future.
This article deals with the development of health law in Europe, and in particular with its future: what challenges are waiting us and are we able to cope with them? After identifying what makes health law different from other disciplines, the first part discusses how it has developed and where we stand now, both at the national and at the European level. The second part focuses on the future. After touching upon a number of societal developments and the increasing 'Europeanisation' and globalisation of health issues, it addresses the question how we should anticipate the challenges ahead.


[Screening and follow-up for congenital heart disease in children aged 0-3 years in rural areas of Chongqing, China].
To examine the incidence of congenital heart disease (CHD) in children aged 0-3 years in the rural areas of Chongqing, and to determine the suitable "screening-diagnosis-follow-up" system and screening indicators for CHD in these areas. Children aged 0-3 years from rural areas of the Fuling Disctrict of Chongqing were selected by cluster sampling. Using the "screening-diagnosis-evaluation system" employed at the levels of village/town, district/county, and province/city, the children were screened for seven indicators, i.e., family history of CHD, dyspnea, cyanosis, unique facial features, other congenital malformations, heart murmurs, and blood oxygen saturation (SpO2<95%). Children who were positive for one or more indicators accepted echocardiography (ECG) for the diagnosis of CHD. CHD patients were evaluated for disease progression, given guided treatments, and followed-up by pediatric cardiologists. Screening was performed for 10 005 out of the 10 281 children enrolled in the study (97.32% response rate). Among the 175 children who were positive for the indicators, 166 underwent ECG and 60 (0.6‰) were diagnosed with CHD, including 46 cases of simple CHD (76.65%), 11 cases of combined CHD (18.33%), and 3 cases of complex CHD (5.00%). Of the 7 screening indicators, heart murmur had the largest area under the ROC curve for the diagnosis of CHD. In addition, a combination of screening indicators (heart murmur, unique facial features, and other congenital malformations) was most effective for screening out CHD. The CHD patients were given surgical or intervention treatments, and followed up for 6 to 18 months. Ten patients improved without treatment, 13 patients received interventional or surgical treatment, 1 patient died of non-cardiac reasons. The remaining 36 patients were subjected to further follow-up. Heart murmur alone and in combination with unique facial features and other congenital malformations are valuable tools for CHD screening in children aged 0-3 years. The "village/town-district/county-province/city" screening-diagnosis-evaluation systems are useful for the early detection, diagnosis, and treatment of CHD in infants and young children from the rural areas of Chongqing.


Role of beta-defensin 2 and interleukin-4 receptor as stroke outcome biomarkers.
Acute ischemic stroke is a complex disease with huge interindividual evolution variability that makes challenging the prediction of an adverse outcome. Our aim was to study the association of bloodstream signatures to early neurological outcome after stroke, by combining a subpooling of samples strategy with protein array discovery approach. Plasma samples from 36 acute stroke patients (< 4.5 h from onset) were equally pooled within outcome groups: worsening, stability, and improvement (n = 3 pools of four patients each, for each outcome group). These nine pools were screened using a 177 antibodies library, and 35 proteins were found altered regarding outcome classification (p < 0.1). Processes of inflammation, immune response, coagulation, and apoptosis were regulated by these proteins. Ten representative candidates, mainly cytokines and chemokines, were assayed for replication in individual baseline plasma samples from 80 new stroke patients: β-defensin2, MIP-3b, plasminogen activator inhibitor 1 active, β-cell-attracting chemokine 1, Exodus-2, interleukin-4 receptor (IL-4R), IL-12p40, leukemia inhibitor factor, MIP-1b, and tumor necrosis factor-related weak inducer of apoptosis. Multivariate logistic regression analysis showed β-defensin 2 (ORadj 4.87 [1.13-20.91] p = 0.033) and IL-4R (ORadj 3.52 [1.03-12.08] p = 0.045) as independent predictors of worsening at 24 h after adjustment by clinical variables. Both biomarkers improve the prediction by 19% as compared to clinical information, suggesting a potential role for risk stratification in acute thrombolyzed stroke patients. Early neurological deterioration after stroke is not easily predictable. The use of blood biomarkers might help in decision-making processes regarding this complication. By combining a sub-pooling of samples strategy with protein array discovery approach, we have found two new biomarkers: beta-defensin-2 and interleukin-4 receptor. Both biomarkers improve the prediction of poor-outcome over clinical variables in the acute phase of stroke.


Objective and subjective prior distributions for the Gompertz distribution.
This paper takes into account the estimation for the unknown parameters of the Gompertz distribution from the frequentist and Bayesian view points by using both objective and subjective prior distributions. We first derive non-informative priors using formal rules, such as Jefreys prior and maximal data information prior (MDIP), based on Fisher information and entropy, respectively. We also propose a prior distribution that incorporate the expert's knowledge about the issue under study. In this regard, we assume two independent gamma distributions for the parameters of the Gompertz distribution and it is employed for an elicitation process based on the predictive prior distribution by using Laplace approximation for integrals. We suppose that an expert can summarize his/her knowledge about the reliability of an item through statements of percentiles. We also present a set of priors proposed by Singpurwala assuming a truncated normal prior distribution for the median of distribution and a gamma prior for the scale parameter. Next, we investigate the effects of these priors in the posterior estimates of the parameters of the Gompertz distribution. The Bayes estimates are computed using Markov Chain Monte Carlo (MCMC) algorithm. An extensive numerical simulation is carried out to evaluate the performance of the maximum likelihood estimates and Bayes estimates based on bias, mean-squared error and coverage probabilities. Finally, a real data set have been analyzed for illustrative purposes.


Advances in the Diagnosis and Treatment of Acute Kidney Injury in Cirrhosis Patients.
Liver cirrhosis is a common progressive and chronic clinical liver disease. Due to the strong compensation ability of the liver, no obvious symptoms develop in the early stage. However, multiple systems are involved in decompensation of the liver. Acute kidney injury (AKI) is one of the most serious complications, characterized by a sharp drop in the glomerular filtration rate (GFR); a rapid increase in Scr and BUN, as well as sodium and water storage; and a disturbance of acid-base balance. The mortality rate is high, and the prognosis is very poor. Thus, it is important to make a definite diagnosis and initiate treatment in the early stage to decrease mortality and improve the prognosis. Although diagnosing liver cirrhosis with serum creatinine has many shortcomings, a dynamic change in this marker is still the main diagnostic criterion for AKI. Identifying new markers of kidney injury with clinical value has also become an increasing focus of research. In this text, we review recent changes regarding categorization of AKI diagnostic criteria as well as new markers of AKI and treatments for cirrhosis-related AKI.


[Gliomas: fighting until the end against epilepsy; administration of antiepileptic drugs in the end-of-life phase].
In patients with high-grade glioma seizures occur relatively frequently during the end-of-life phase. At some point, the use of oral anti-epileptic drugs is no longer possible due to swallowing difficulties caused by advanced tumour progression. We have established a draft guideline and propose that anti-epileptic drugs be prescribed by alternative routes of administration in the end-of-life phase in glioma patients with known epilepsy who develop swallowing difficulties. Buccal clonazepam would be our drug of first choice as a maintenance treatment in addition to intranasal midazolam for the acute management of seizures. Adequate treatment of epileptic seizures, particularly during the end-of-life phase, can help to maintain quality of life as long as possible in patients with high-grade glioma.


Immunoexpression of NF-ĸB and their inhibitory subunits IĸBα and IĸBβ in giant cell lesions of the jaws: implications for their clinical behavior.
The unpredictable behavior of giant cell lesions (GCLs) of the jaws parallels its controversial histogenesis. This study evaluated a possible association between the immunohistochemical expression of NF-ĸB, the inhibitory subunits IĸBα/IĸBβ, and clinicopathological variables with the behavior of central and peripheral GCLs of the jaws. Paraffin-embedded samples of GCLs of the jaws (n = 68) were prepared for histological/immunohistochemical assessment. Demographic and clinicopathological parameters were assessed to determine the behavior of the lesions. A staining-intensity-distribution (SID) score was used to assess the immunomarkers reactivity. The association between significant candidate immunohistochemical predictor variables regarding clinical behavior was analyzed individually and adjusted for confounding using a binary logistic regression model. While univariate analysis revealed a positive association of NF-ĸB SID score, NF-ĸB nuclear expression, IĸBα SID score, and NF-ĸB to inhibitors average ratio with the aggressive status of GCLs, after bivariate logistic regression analysis, only NF-ĸB nuclear expression, IĸBα SID score, and NF-ĸB to inhibitors average ratio remained as robust predictors of aggressiveness. Confounding and interaction effects regarding clinicopathological candidate predictor variables were also noted. It looks that clinical behavior of GCLs of the jaws may be strong/independently linked to the increased nuclear expression of NF-ĸB, higher NF-ĸB to inhibitors average ratio, and decreased IĸBα SID score. Notwithstanding, there are simultaneously synergistic and opposing interactive effects with respect to age stratum, growth rate, multinucleated giant cells count, and mononuclear stromal cells density in the susceptible host that may increase the tissue destruction observed in aggressive GCLs.


Customer engagement in innovative smart grid deployment projects: evidence from Russia.
In recent years, Russian power grid companies have significantly intensified their planning and implementing innovative projects to introduce various elements of smart grid technology. The global experience shows that the best potential outcome from smart grid technologies largely relies on the customers' readiness and adoption. To this end, we assess the Russian consumers' awareness and readiness regarding smart grid technologies by conducting a comprehensive survey. Our empirical study showed that, in general, Russian consumers are unaware of the various aspects of smart grid technologies. On the contrary, a significant share of respondents believes that smart grid technologies can reduce their energy consumption burden through gaining efficiency. The low level of awareness would be detrimental to accrue smart grid innovative projects' potential socio-economic and environmental benefits. We propose several recommendations for policymakers and managers of grid companies for the elimination of the identified risks.


Moderate inappropriately high aldosterone/NaCl constellation in mice: cardiovascular effects and the role of cardiovascular epidermal growth factor receptor.
Non-physiological activation of the mineralocorticoid receptor (MR), e.g. by aldosterone under conditions of high salt intake, contributes to the pathogenesis of cardiovascular diseases, although beneficial effects of aldosterone also have been described. The epidermal growth factor receptor (EGFR) contributes to cardiovascular alterations and mediates part of the MR effects. Recently, we showed that EGFR is required for physiological homeostasis and function of heart and arteries in adult animals. We hypothesize that moderate high aldosterone/NaCl, at normal blood pressure, affects the cardiovascular system depending on cardiovascular EGFR. Therefore we performed an experimental series in male and female animals each, using a recently established mouse model with EGFR knockout in vascular smooth muscle cells and cardiomyocytes and determined the effects of a mild-high aldosterone-to-NaCl constellation on a.o. marker gene expression, heart size, systolic blood pressure, impulse conduction and heart rate. Our data show that (i) cardiac tissue of male but not of female mice is sensitive to mild aldosterone/NaCl treatment, (ii) EGFR knockout induces stronger cardiac disturbances in male as compared to female animals and (iii) mild aldosterone/NaCl treatment requires the EGFR in order to disturb cardiac tissue homeostasis whereas beneficial effects of aldosterone seem to be independent of EGFR.


Synthesis of phenoxyacetic acid derivatives as highly potent antagonists of gastrin/cholecystokinin-B receptors.
A novel series of phenoxyacetic acid derivatives was synthesized based on considerations of the three-dimensional structural similarity of YM022 and RP72540. The gastrin/cholecystokinin (CCK)-B and CCK-A receptor antagonist activities of these compounds were evaluated by investigation of their affinities for human gastrin/CCK-B receptors and human CCK-A receptors, respectively. It was found that N-methyl-N-phenyl-2-[2-[N-(N-methyl-N-phenyl-carbamoylmethyl)-N-[2 -[3-(3- methylphenyl)ureido]acetyl]amino]phenoxy]acetamide (20k, DZ-3514) exhibited high affinity for gastrin/CCK-B receptors and high selectivity over CCK-A receptors.


The impact on prevalence of dementia in the oldest age groups of differential mortality patterns: a deterministic approach.
Until recently relatively little data have been available on the prevalence of dementia in the oldest age groups, and yet it is these age groups which are expanding fastest. It is therefore important to understand whether the prevalence of dementia rises inexorably with age ('age-dependent'), or, as some suggest, levels off or even declines in the very oldest age groups ('age-related'). Combined analysis of the many prevalence studies now available has led to modelled curves which do suggest a slowing of rise in prevalence at these great ages, and has been interpreted as meaning that dementia is age-related. This interpretation does not take into account the differential survival of individuals with cognitive impairment compared with normals of the same age. Flexible prevalence-incidence-duration models were generated using a deterministic approach applied to published combined analyses of prevalence rates, population death rates and mortality odds ratios. The variation in observed prevalence patterns with age is explained to a great extent by the mortality observed in the cognitively impaired. Simple examination of age patterns in prevalence does not answer the fundamental question surrounding the age-dependence of cognitive impairment. Inferring biological meaning from these observed curves is not valid without examining the mathematical phenomena of the relationship of incidence, mortality and prevalence. This approach allows an examination of the impact of varying mortality and incidence on the prevalence of dementia and cognitive impairment and will be useful in determining the potential impact of preventive strategies on the population.


Cost Analysis of Developing, Implementing, and Evaluating a Multi-Disciplinary Teaching Kitchen.
Teaching kitchens have emerged as strategies to deliver lifestyle medicine principles and practices. However, a better understanding of their implementation, delivery cost, and potential benefits are needed. This article provides a comprehensive analysis of the costs associated with the development, deployment, and evaluation of the Emory Healthy Kitchen Collaborative (EHKC) teaching kitchen clinical trial. The actual number of hours spent and costs incurred to develop and deploy the EHKC teaching kitchen were recorded and broadly categorized into 1 of 4 areas: program development, course delivery, research, and optional enhancements. Costs of each item were assigned as fixed or variable, enabling calculation of the marginal per participant program cost. Total costs were US$123,898, with 3/4 incurred for program development, research, and optional enhancements. Delivery of the course alone (not including program development costs, research, or any optional enhancements) cost US$30,194. The total cost per participant for the course was US$755, with a marginal participant cost of US$141. Teaching kitchens represent viable options to deliver lifestyle medicine interventions. However, more research and cost analyses are needed to better understand the value teaching kitchens provide to determine if they are an effective and economical way to deliver lifestyle medicine.


Shift in the Light Quality of Night Interruption Affects Flowering and Morphogenesis of Petunia hybrida.
Petunia hybrida Hort. "Easy Wave Pink", a qualitative long-day plant (LDP), was investigated to study the effects of the night interruption light (NIL) provided by light-emitting diodes (LEDs) quality shifting on the morphogenesis, blooming, and transcription of photoreceptor genes. Plants were grown in a closed-type plant factory employing white (W) LEDs at an intensity of 180 μmol·m-2·s-1 PPFD provided for short day (SD, 10 h light, 14 h dark), long day (LD, 16 h light, 8 h dark), or SD with 4 h night interruption (NI) with LEDs at an intensity of 10 μmol·m-2·s-1 PPFD. The NIL quality was shifted from one light spectrum to another after the first 2 h of NI. Light treatments consisting of all possible pairings of W, far-red (Fr), red (R), and blue (B) light were tested. The SD and LD were referenced as the control, while 12 NI treatments involved altering LED NIL qualities, as follows: from R to B (NI-RB), from B to R (NI-BR), from Fr to R (NI-FrR), from R to Fr (NI-RFr), from Fr to B (NI-FrB), from B to Fr (NI-BFr), from B to W (NI-BW), from W to B (NI-WB), from W to Fr (NI-WFr), from Fr to W (NI-FrW), from W to R (NI-WR), and from R to W (NI-RW). The NI-RFr resulted in the longest shoots, while the NI-WR and NI-RW resulted in the shortest shoots. NI-WR, NI-RW, NI-BW, NI-WB, NI-RFr, NI-RB, NI-BR, and LD all exhibited flowering. High-level expressions of photoreceptor genes were confirmed in the NI-RFr, NI-FrR, NI-BFr, NI-RW, and NI-WR treatments. Morphogenesis and blooming were both impacted by the photoperiod. The first NIL had no effects on the flowering or the morphogenesis, but the second NIL had a profound impact on both.


Improvement of Immunosuppressive Medication Adherence Using a SystemCHANGE Intervention: Case Study of an Older Adult Kidney Transplant Recipient.
This article reports a case study of an older adult kidney transplant recipient with poor medication adherence enrolled in an innovative six-month SystemCHANGE intervention that seeks to systematically improve medication adherence by identifying and shaping routines, involving others in routines, and using medication-taking feedback through small, patient-led experiments. Medication adherence increased immediately and was sustained throughout the intervention and maintenance phases. This is the first case study to demonstrate effectiveness of the SystemCHANGE intervention for promoting medication adherence in a kidney transplant recipient. The intervention improved the timing of doses by linking them to a regularly occurring behavior and providing feedback. The SystemCHANGE intervention represents a systems-thinking approach for both provider and patients, and gives healthcare providers the tools needed to assist patients in using habits and routines, and feedback to improve medication taking and timing.


Ca2+-related regulatory function of fibrinogen.
Fibrinogen displays a regulation of considerable physiological significance by lowering the Ca2+ requirement for the conversion of the fibrin-stabilizing factor (Factor XIII) zymogen to the range of concentrations of this ion found in plasma. Fibrinogen modulates both Ca2+-dependent steps in the complex process of zymogen activation, involving the heterologous dissociation of subunits of the thrombin-modified zymogen (Factor XIII') species : formula: (see text) and the unmasking of iodoacetamide titratable sites during generation of transamidating activity : formula: (see text). It is interesting that a thrombin-independent pathway of zymogen activation : formula: (see text), which we found to operate at Ca2+ concentrations above 50 mM, is not affected by the presence of fibrinogen. Regulation by fibrinogen thus appears to be specific for controlling only the physiological pathway of zymogen conversion.


The structure of human microplasmin in complex with textilinin-1, an aprotinin-like inhibitor from the Australian brown snake.
Textilinin-1 is a Kunitz-type serine protease inhibitor from Australian brown snake venom. Its ability to potently and specifically inhibit human plasmin (K(i) = 0.44 nM) makes it a potential therapeutic drug as a systemic anti-bleeding agent. The crystal structures of the human microplasmin-textilinin-1 and the trypsin-textilinin-1 complexes have been determined to 2.78 Å and 1.64 Å resolution respectively, and show that textilinin-1 binds to trypsin in a canonical mode but to microplasmin in an atypical mode with the catalytic histidine of microplasmin rotated out of the active site. The space vacated by the histidine side-chain in this complex is partially occupied by a water molecule. In the structure of microplasminogen the χ(1) dihedral angle of the side-chain of the catalytic histidine is rotated by 67° from its "active" position in the catalytic triad, as exemplified by its location when microplasmin is bound to streptokinase. However, when textilinin-1 binds to microplasmin the χ(1) dihedral angle of this amino acid residue changes by -157° (i.e. in the opposite rotation direction compared to microplasminogen). The unusual mode of interaction between textilinin-1 and plasmin explains textilinin-1's selectivity for human plasmin over plasma kallikrein. This difference can be exploited in future drug design efforts.


Nanoenhanced hydrogel system with sustained release capabilities.
An alginate/halloysite nanotube (HNT) nanocomposite was developed with sustained release of bone morphogenetic proteins (BMPs) at picogram low levels. BMP-2, 4, and 6 and osteoblasts were chosen as our model "growth factor" and "cell type" as the interaction of BMPs with osteoblasts is well known and thoroughly investigated. Alginate hydrogels with HNTs doped with BMP-2, 4, or 6 only or BMP-4 and 6 in combination. Osteoblasts were seeded within the hydrogels and studied for changes in cell proliferation, phenotypic expression, and mineralization over a 28-day experimental period. Osteoblast behavior was enhanced in BMP doped hydrogel/HNTs nanocomposites as compared with control groups. Release profiles showed that BMP-2 was released in a sustained fashion over a 7-day period and at picogram levels. Mineralization, as showed by Von Kossa staining, and protein synthesis peaked at 28 days, for all three growth factor combinations. BMP-4 provided a marked stimulus for osteoblast functionality base and was comparable to BMP-6 in terms of osteoblast differentiation and mineralization. BMP-4 and 6, in combination, showed a marked enhancement in osteoblast differentiation and functionality; however, the response seemed to be delayed when compared with BMP-4 and 6 release. Hydrogel surfaces had a complex surface topography and greater structural integrity with increased halloysite addition. The data suggest that these nanocomposites may provide a mechanism to enhance repair and regeneration in damaged or diseased tissues, reducing the need for more invasive treatment modalities.


CT imaging spectrum of infiltrative renal diseases.
Most renal lesions replace the renal parenchyma as a focal space-occupying mass with borders distinguishing the mass from normal parenchyma. However, some renal lesions exhibit interstitial infiltration-a process that permeates the renal parenchyma by using the normal renal architecture for growth. These infiltrative lesions frequently show nonspecific patterns that lead to little or no contour deformity and have ill-defined borders on CT, making detection and diagnosis challenging. The purpose of this pictorial essay is to describe the CT imaging findings of various conditions that may manifest as infiltrative renal lesions.


Production of lexical categories in French children with SLI and in normally developing children matched for MLU.
Free speech recording samples of two groups of French SLI children aged 48 and 62 months (matched for MLU, 1.70) and two groups of French normally developing children aged 26 and 36 month (matched for MLU, 3.2) were compared to determine whether they showed a difference in the use of lexical categories. A category-by-category comparison showed few significant differences. For low MLU children, SLI produced significantly fewer infinitives, past participles, copulas, and demonstrative pronouns. For high MLU children, the difference persisted only in past participles use. As for English SLI children, French SLI children were delayed in their acquisition of verbs. However, the differences in the syntactic structure of English and French ruled out a syntactic explanation of the deficit. Phonetic problems seem to decrease with age, so they cannot be the only explanation behind the difficulties of SLI children, which probably involve cognitive problems such as processing limitations.


Lung to head ratio in infants with congenital diaphragmatic hernia does not predict long term pulmonary hypertension.
Lung-to-head ratio (LHR) has been used for antenatal evaluation of infants with congenital diaphragmatic hernia (CDH). We hypothesized that LHR was predictive of acute and chronic pulmonary hypertension in infants with CDH. Echocardiograms on all inborn infants with CDH (December 2001-March 2011) were reviewed. Echocardiograms at 1 and 3 months post-repair and most recent follow-up were assessed for presence of pulmonary hypertension (PAH). LHR, gestational age, birth weight, extracorporeal membrane oxygenation (ECMO), and death rate were obtained. Bivariate and multivariate analyses were performed. 106 infants with CDH had LHR obtained at median 28 weeks gestation (median LHR=1.25 [range 0.4-5.3]). Median follow-up was 26.6 months (range 4.6-97.5). The long-term incidence of pulmonary hypertension was 16%. LHR was significantly associated with pulmonary hypertension at one month (p=0.0001) but not at 3 months (p=0.22) or long-term (p=0.54). LHR was predictive of ECMO use (p=0.01) and death (p=0.001). The overall incidence of PAH in infants with CDH decreases over time. Prenatal LHR predicts PAH at one month but not long-term in infants with CDH. The ability for LHR to predict PAH at one month but not long term may suggest remodeling of the pulmonary vasculature over time.


Efficacy of skin preparation solutions in patients with total knee replacement: A randomized controlled trial.
Surgical site infection following total knee replacement is considered as one of the most severe postoperative complications. The presence of bacteria at the surgical site is the most important risk factor and therefore it is essential to prevent infection through appropriate preoperative skin preparation. The purpose of this study was to examine the presence and type of native bacteria on the incision site and to assess which skin preparation is most effective to sterilize those native bacteria. Scrub-and-paint 2 step method was used for standard preoperative skin preparation. 150 patients who underwent total knee replacement were grouped into 3 groups- Group 1 (povidone-iodine scrub-and-paint), Group 2 (chlorhexidine gluconate paint after povidone-iodine scrub), and Group 3 (povidone-iodine paint after chlorhexidine gluconate scrub). 150 specimens of post-preparation swabs were obtained and cultured. To analyze the native bacteria at the total knee replacement incision site, 88 additional swaps were performed before skin preparation and cultured. The positive rate of bacterial culture after skin preparation was 5.3% (8/150). Positive rates of the groups were 12% (6/50) in group 1, 2% (1/50) in group, 2 and 2% (1/50) in group 3 and positive rates of bacterial culture after skin preparation in group 2 and group 3 were lower than in group 1 (p = 0.037). Among the 55 patients who had positive bacterial culture prior to skin preparation, 26.7% (4/15) in group 1, 5.6% (1/18) in group 2, and 4.5% (1/22) in group 3 were positive. Group 1 showed 7.64 times higher positive bacterial culture rate after skin preparation than group 3 (p = 0.084). During skin preparation prior to total knee replacement surgery, chlorhexidine gluconate paint after povidone-iodine scrub or povidone-iodine paint after chlorhexidine gluconate scrub had a superior effect on sterilizing native bacteria compared to povidone-iodine scrub-and-paint method.


Diversity of Alkylproline Moieties in Pyrrolobenzodiazepines Arises from Postcondensation Modifications of a Unified Building Block.
Anticancer pyrrolobenzodiazepines (PBDs) are one of several groups of natural products that contain unusual 4-alkyl-l-proline derivatives (APDs) in their structure. APD moieties of PBDs are characterized by high structural diversity achieved through unknown biosynthetic machinery. Based on LC-MS analysis of culture broths, feeding experiments, and protein assays, we show that APDs are not incorporated into PBDs in their final form as was previously hypothesized. Instead, a uniform building block, 4-propylidene-l-proline or 4-ethylidene-l-proline, enters the condensation reaction. The subsequent postcondensation steps are initiated by the introduction of an additional double bond catalyzed by a FAD-dependent oxidoreductase, which we demonstrated with Orf7 from anthramycin biosynthesis. The resulting double bond arrangement presumably represents a prerequisite for further modifications of the APD moieties. Our study gives general insight into the diversification of APD moieties of natural PBDs and provides proof-of-principle for precursor directed and combinatorial biosynthesis of new PBD-based antitumor compounds.


Coordination-Driven Folding in Multi-ZnII -Porphyrin Arrays Constructed on a Pillar[5]arene Scaffold.
Pillar[5]arene derivatives bearing peripheral porphyrin subunits have been efficiently prepared from a deca-azide pillar[5]arene building block (17) and ZnII -porphyrin derivatives bearing a terminal alkyne function (9 and 16). For the resulting deca-ZnII -porphyrin arrays (18 and 20), variable temperature NMR studies revealed an intramolecular complexation of the peripheral ZnII -porphyrin moieties by 1,2,3-triazole subunits. As a result, the molecules adopt a folded conformation. This was further confirmed by UV/Vis spectroscopy and cyclic voltammetry. In addition, we have also demonstrated that the coordination-driven unfolding of 18 and 20 can be controlled by an external chemical stimulus. Specifically, addition of an imidazole derivative (22) to solution of 18 or 20 breaks the intramolecular coordination at the origin of the folding. The resulting molecular motions triggered by the addition of the imidazole ligand mimic the blooming of a flower.


Sub-cellular mRNA localization modulates the regulation of gene expression by small RNAs in bacteria.
Small non-coding RNAs can exert significant regulatory activity on gene expression in bacteria. In recent years, substantial progress has been made in understanding bacterial gene expression by sRNAs. However, recent findings that demonstrate that families of mRNAs show non-trivial sub-cellular distributions raise the question of how localization may affect the regulatory activity of sRNAs. Here we address this question within a simple mathematical model. We show that the non-uniform spatial distributions of mRNA can alter the threshold-linear response that characterizes sRNAs that act stoichiometrically, and modulate the hierarchy among targets co-regulated by the same sRNA. We also identify conditions where the sub-cellular organization of cofactors in the sRNA pathway can induce spatial heterogeneity on sRNA targets. Our results suggest that under certain conditions, interpretation and modeling of natural and synthetic gene regulatory circuits need to take into account the spatial organization of the transcripts of participating genes.


In vivo imaging of proteasome inhibition using a proteasome-sensitive fluorescent reporter.
A proteasome degrades numerous regulatory proteins that are critical for tumor growth and is therefore recognized as a promising anticancer target. Determining proteasome activity in the tumors of mice bearing xenografts is essential for the development of novel proteasome inhibitors. We developed a system for in vivo imaging of proteasome inhibition in the tumors of living mice, using a proteasome-sensitive fluorescent reporter, ZsProSensor-1. This reporter consists of a green fluorescent protein, ZsGreen, fused to mouse ornithine decarboxylase, which is degraded by the proteasome without being ubiquitinated. In stably transfected cells expressing ZsProSensor-1, the fluorescent reporter was rapidly degraded under steady-state conditions, whereas it was stabilized in the presence of proteasome inhibitors. Subcutaneous inoculation of the transfected cells into nude mice resulted in tumor formation. When the proteasome inhibitor bortezomib was intravenously administered to mice bearing these tumors, the ZsProSensor-1 protein accumulated in the tumors and emitted a fluorescent signal in a dose-dependent manner. Robust fluorescence was sustained for 3 days and then gradually decreased to baseline levels within 15 days. Intravenous administration of bortezomib also showed potent antitumor activity. In contrast, oral administration of bortezomib did not result in fluorescent protein accumulation in tumors or exhibit any antitumor activity. These results indicate that in vivo imaging using the ZsProSensor-1 fluorescent protein can be used as an indicator of antitumor activity and will be a powerful tool for the development of novel proteasome inhibitors.


Management of native warm-season grasses for beef cattle and biomass production in the Mid-South USA.
Native grasses, such as switchgrass (SG; L.), big bluestem (BB; Vitman), indiangrass (IG; Nash), and eastern gamagrass (EG; [L.] L.) may be capable of providing desirable summer forage for cattle as well as a source of biomass for renewable energy. To evaluate that potential, experiments were conducted at 2 locations in Tennessee comparing weaned beef () steers (268 ± 25 kg initial BW) during early-season grazing (Early; 30 d, typically corresponding to May, followed by postdormancy biomass harvest) and full-season grazing (Full, mean duration = 98 d). For Exp. 1, which compared SG, a blend of BB and IG (BBIG), and EG, ADG was greater ( < 0.05) for BBIG (1.02 kg/d) than SG (0.85 kg/d), and both were greater ( < 0.05) than EG (0.66 kg/d). Grazing days for SG and EG were similar (389 and 423 animal unit days [AUD]/ha, respectively) and exceeded ( < 0.05) that of BBIG (233 AUD/ha) during Full. In Exp. 2 (SG and BBIG only), rates of gain were comparable to that of Exp. 1, but AUD were 425 (SG) and 299 (BBIG) AUD/ha. Such rates of gain and grazing days indicate that these grasses can provide desirable summer forage for growing cattle. Early produced 211 to 324 kg BW gain/ha, depending on experiment and forage, followed by dormant-season harvests of 7.5 to 10.5 Mg/ha of biomass, indicating a potential for beef cattle forage and biomass production on the same land resource. Native grasses provided productive summer pasture and good rates of gain on growing cattle and could contribute to forage programs, especially where cool-season grasses currently predominate.


Thoracic aortic compliance as a determinant of rupture of abdominal aortic aneurysms.
The relative importance of collagen and elastin in formation, expansion, and rupture of abdominal aortic aneurysms (AAAs) has been investigated extensively. Aortic compliance, which is a relevant component of cardiac afterload, is also determined by the relative amount of media proteins in large arteries as well as by pathological arterial processes. The objective of this study was to determine if thoracic aortic compliance was different in patients with ruptured AAAs compared to those undergoing elective AAA repair. The study was carried out in 43 patients with infrarenal AAAs in the postoperative period. The first group (A) included 17 patients undergoing emergency ruptured AAA repair. The second group (B) included 26 patients operated on for an AAA who underwent elective repair. Patients were studied by a noninvasive Doppler echocardiography. Pulse wave velocity (PWV) was determined in the descending thoracic aorta. Results show that patients with electively repaired AAAs had an accelerated pulse wave transmission, typical of an atherosclerotic aorta with a Gaussian distribution (PWV 9.26 m/sec +/- 1.27). In contrast, patients with ruptured aneurysms presented in a distribution with three peaks. A striking increase in aortic compliance (41% of patients with PWV<6 m/sec in group A vs. 3% of group B) was observed in patients with ruptured AAAs.


Lessons learned from hybrid surgery with preoperative coil embolization for an aberrant artery in pulmonary sequestration.
The optimal management of an aberrant artery in pulmonary sequestration (PS) is controversial. Several studies have shown that hybrid surgery with preoperative coil embolization for an aberrant artery and surgical resection of the sequestrated lung is effective. However, there are no clear indications for the procedure. A 68-year-old woman without any complaints was diagnosed with right intralobar PS, which was supplied by an aberrant artery from the thoracic aorta, via computed tomography performed during a medical examination. In addition, lung adenocarcinoma was detected over the border between the right upper and middle lobes. Preoperative coil embolization was performed by an interventional radiologist the day before surgery to decrease the risk of severe intraoperative hemorrhage. On the following day, bi-lobectomy of the right upper and middle lobes for lung adenocarcinoma with systemic lymph node dissection and segmentectomy of the sequestrated lung with thoracotomy was performed. Although no active hemorrhage was observed during surgery, the aberrant artery was challenging to dissect using an energy device due to the presence of an intravascular coil. Eventually, the coil stump was exposed, and it was cut with scissors. The postoperative course was uneventful. We reported the pitfall of the hybrid surgery for intralobar PS. Preoperative coil embolization can prevent fatal intraoperative hemorrhage. If embolization is performed using a coil for an aberrant artery supplied from the thoracic aorta, where and how to dissect the aberrant artery should be cautiously determined based on preoperative images, with consideration of the presence of an intravascular coil.


FDG-PET/CT of head and neck squamous cell carcinoma in a rat model.
The aim of this study was to demonstrate the ability to use human clinical positron emission tomography/computed tomography (PET/CT) to detect and investigate head and neck cancers chemically induced by 4-nitroquinoline-1-oxide (4-NQO) in a rat model. The study design was prospective animal research. A head and neck squamous cell carcinoma was established in 20 immunocompetent rats, who drank a 4-NQO solution during 16 weeks. 2-Deoxy-2-[F-18]fluoro-D: -glucose (FDG)-PET/CT was performed for five of them, 34 weeks after the start of the experiment to characterize the tumors. A day following the FDG-PET/CT, rats were euthanized and pathological features were evaluated by hematoxylin-eosin staining. All rats had head and neck tumor at various locations at 34 weeks. Among the five rats selected for having FDG-PET/CT, the clinical examination detected exophytic tumors grown in the oral cavity for three of them (one on the inferior lip, one on the hard palate, and one on the internal side of the cheek). FDG-PET/CT confirmed the presence of those tumors and detected ones located on the base of tongue for three of them. Tumor extensions were characterized and tumor metabolic volumes were measured. The smallest lesion detected measured 3 x 3 x 4 mm. Pathologic examination using hematoxylin-eosin staining confirmed squamous cell carcinoma. This study demonstrated that FDG-PET/CT is a feasible examination to detect occult primary tumors in rat models. It is useful to follow tumor progression and evaluate therapeutics efficacy.


Inhibition of protein synthesis in noninfected L cells by partially purified interferon preparations.
Partially purified interferon preparations, obtained from L-cell monolayers infected with Newcastle disease virus (NDV), were shown to inhibit protein synthesis in noninfected L cells. The incorporation of several amino acids-(14)C was equally sensitive to the pretreatment of the cells with the interferon preparation. Treatment of L-cell monolayers for 24 hr with 800 units of interferon resulted in a 50% decrease in amino acid incorporation. The degree of inhibition was found to be a function of the interferon concentration and the time of exposure of the cells to the partially purified preparations. No inhibitory effect was detected in medium obtained from noninfected cells and purified in an identical manner. The inhibitory effect was shown to be cell specific in that the partially purified interferon from L cells did not reduce amino acid incorporation in heterospecific cell lines. Heating the interferon preparations at 60 degrees C destroyed their antiviral activity and their ability to inhibit valine-(14)C incorporation in L cells.


Aldosterone activates Na+/H+ exchange and raises cytoplasmic pH in target cells of the amphibian kidney.
The hypothesis was tested if the mineralocorticoid hormone aldosterone stimulates Na+/H+ exchange in "giant cells" fused from individual target cells of the distal nephron of the frog kidney. By means of microelectrodes, steady-state intracellular pH (pHi) and pHi recovery from an acid load were recorded continuously while the fused cells were exposed to aldosterone. Twenty minutes after addition of the hormone, pHi started to rise and reached a new steady state after about 60 min (delta pHi = 0.28 +/- 0.01). After hormone treatment, pHi recovered significantly faster in response to an intracellular acid load. The diuretic drug amiloride blocked pHi recovery. Experiments in intact tubules showed that aldosterone induces H+ and K+ secretion. Thus, intracellular alkalosis, mediated by Na+/H+ exchange, could serve as a signal that activates pH-sensitive K+ channels of the luminal cell membrane.


[Use of glidewires in urology. Note on endourological technique].
In urology, the use of angiographic wires (glidewires) allows the anterograde, retrograde and "mixed" approach in obstructive and not obstructive uropathies stenting. The Authors reported a case of oligoanuria in a patient with progressing prostatic cancer resolved with endoscopical recanalization and secondary indwelling double-J ureteral stenting.


Overview of determination of biopharmaceutical properties for development candidate selection.
The physicochemical and biopharmaceutical properties of putative drug molecules impact their performance in both in vitro and in vivo studies. The design and selection of molecules with drug-like properties assists in the selection of drug candidates with a higher probability of success in the development process. Described in this overview are commonly used approaches for measuring compound solubility, permeability, and partitioning in drug discovery and development. The utility of these methods in the drug discovery process and product development is discussed. The evaluation of crystallinity and physicochemical stability in relation to biopharmaceutical properties and in assessing the potential for successful development are also discussed.


Pediatric burn care: new techniques and outcomes.
Thermal injury is a leading cause of morbidity and mortality in children. This review highlights the current management of thermal injury and its complications. Many recent advances in burn care have improved the outcomes of patients with thermal injury; however, variability does exist, and there are many opportunities for improvement. This review will highlight the complexity of issues encountered along the continuum of care for thermal injury patients. Accurate estimation of total burn surface area (TBSA) of a burn continues to be a challenge in pediatric patients. Variability continues to exist surrounding the management of burn resuscitation and complex wounds. Children with extensive burns have profound immune and metabolic changes that can lead to multiple complications, including infections, growth arrest, and loss of lean body mass. Standardization in measurements related to quality of life and psychological stress following pediatric thermal injury is much needed. The care of pediatric patients with thermal injury is complex and multifaceted. This review highlights the most recent advances in pediatric burn care.


Novel Isosteviol-Based FXa Inhibitors: Molecular Modeling, In Silico Design and Docking Simulation.
Direct oral anticoagulants are an important and relatively new class of synthetic anticoagulant drugs commonly used for the pharmacotherapy of thromboembolic disorders. However, they still have some limitations and serious side effects, which continuously encourage medicinal chemists to search for new active compounds acting as human-activated coagulation factor X (FXa) inhibitors. Isosteviol is a nontoxic hydrolysis product of naturally occurring stevioside and possesses a wide range of therapeutic properties, including anticoagulant activity. The present contribution describes the in silico design of novel oxime ether isosteviol derivatives as well as a molecular modeling approach based on QSAR analysis and a docking simulation for searching for novel isosteviol-based compounds as potential FXa inhibitors. The elaborated ANN model, encompassing topological and geometrical information, exhibited a significant correlation with FXa-inhibitory activity. Moreover, the docking simulation indicated six of the most promising isosteviol-like compounds for further investigation. Analysis showed that the most promising derivatives contain heterocyclic, aromatic, five-membered moieties, with substituents containing chlorine or fluorine atoms. It is anticipated that the findings reported in the present work may provide useful information for designing effective FXa inhibitors as anticoagulant agents.


[Population study of knowledge and practice in the Albanian population regarding water usage and diarrhea prevention].
The worsening of the social-environmental conditions during the period of transition of Albania and an epidemic of cholera (1994) were the cue for the execution of the study. The main objective is the description of knowledge and attitudes of the Albanian mothers about the risk factors for the gastroenteritis. This is a descriptive study of a representative sample (2100 families) of the population who reside in the central area of Albania, in 1996. The sample has been selected by cluster-sampling method. Interviewers trained previously, collected the data with a questionnaire ad hoc. Data elaboration has been carried out with the software Epilnfo 5. 99.7% (2094) of the enlisted mothers, mean age 28.7 years, were interviewed. 2/3 of them reside in rural areas. We considered social-demographic variables and their relation with the generic hygienic norms and those relative to water, foods, animals. The basic knowledge was very insufficient, particularly in rural areas, and in relation with lower social-economic index and instruction. The study reflects the state of transition train of the political and social-sanitary situation of Albania in the last decade. Still the knowledge and the attitudes about the alimentary hygiene are inadequate. It seems opportune to face this emergency with campaigns aimed at health education and public health interventions.


History of midwifery in New Mexico: partnership between curandera-parteras and the New Mexico Department of Health.
Curandera-parteras (traditional Hispanic midwives) have been in northern New Mexico since before its statehood. In the 1930s, the New Mexico Department of Health began a valuable relationship with the curandera-parteras through the Midwife Consultant Program. This article describes the relationship between the curandera-parteras and the New Mexico Department of Health originating in the 1920s. The amenable and effective working relationship achieved between curandera-parteras and public health during this time period helped create the positive support for midwifery that is apparent in New Mexico today.


The sedimentation coefficient and buoyant density of nucleosomes from replicating chromatin in heated cells.
The sedimentation coefficient and buoyant density of mononucleosomes from the replicating chromatin of heated (45 degrees) and unheated HeLa cells were determined. It was observed that both physical parameters were the same (S = 10.8 and p = 1.165 g/cm3) for nucleosome particles from replicating and mature chromatin in heated and unbeated cells. The size of DNA in the nascent and mature nucleosome from heated or unheated cells was observed to be 145 base pairs of double-stranded DNA. A significant fraction of nucleosomal DNA from heated cells was observed at subnucleosomal sizes, principally at 125 base pairs of DNA. It is concluded that 45 degrees thermal shock does not alter appreciably the subunit structure of chromatin at the replication fork.


Critical illness associated new onset atrial fibrillation: subsequent atrial fibrillation diagnoses and other adverse outcomes.
Amongst patients with critical illness associated new onset AF (CI-NOAF), the risk of subsequent atrial fibrillation (AF) diagnoses and other adverse outcomes is unknown, and the role for long-term anticoagulation is unclear. This study sought to determine the factors associated with subsequent AF diagnoses and other adverse outcomes in this cohort. Admissions to a tertiary general intensive care unit (ICU) between December 2015 and September 2018 were screened for AF episodes through hourly analysis of continuous ECG monitoring. Patients with a prior history of AF were excluded. AF burden was defined as the percentage of monitored ICU hours in AF. The primary endpoint was subsequent AF diagnoses, as collated from the statewide electronic medical records. Secondary endpoints included mortality, embolic events, MACE and subsequent anticoagulation. Of 7030 admissions with 509 303 h of monitoring data, 309 patients with CI-NOAF were identified, and 235 survived to discharge. Subsequent AF diagnoses were identified in 75 (31.9%) patients after a median of 413 days. Increased AF burden had the strongest independent association with AF recurrence (OR = 15.03, P = 0.002), followed by increased left atrial area (OR = 1.12, P = 0.01). Only 128 (54.5%) patients had their AF diagnosis acknowledged at ICU discharge, and 50 (21.3%) received anticoagulation at hospital discharge. CI-NOAF is often under-recognized, and subsequent AF diagnoses are common post-discharge. AF burden during ICU admission has a strong independent association with subsequent AF diagnoses. Left atrial size is also independently associated with subsequent AF.


Tissue engineering: recent advances and review of clinical outcome for urethral strictures.
Urethrotomy remains the first-line therapy in the treatment of a urethral stricture despite data showing no real chance of a cure after repeated urethrotomies. An anastomotic or an augmentation urethroplasty using oral mucosa can be offered to patients following failed urethrotomy. The potential for a tissue engineered solution as an alternative to native tissue has been explored in recent years and is reviewed in this article. More than 80 preclinical studies have investigated a tissue-engineered approach for urethral reconstruction mostly using decellularized natural scaffolds derived from natural extracellular matrix with or without cell seeding. The animal models used in preclinical testing are not representative of disease processes seen with strictures in man. The available clinical studies are based on small noncontrolled series. There is a potential role for tissue engineering to provide a material for substitution urethroplasty and work has demonstrated this. Further work will require a rigorous basic science programme and adequate evaluation of the material prior to its introduction into clinical practice. The research with tissue engineering applied to the urethra has not yet been resulted in a widely available material for clinical use that approaches the efficacy seen with the use of autologous grafts.


Headspace solid-phase microextraction (HS-SPME) combined with GC-MS as a process analytical technology (PAT) tool for monitoring the cultivation of C. tetani.
Vaccine production is a biological process in which variation in time and output is inevitable. Thus, the application of Process Analytical Technologies (PAT) will be important in this regard. Headspace solid - phase microextraction (HS-SPME) coupled with GC-MS can be used as a PAT for process monitoring. This method is suitable to chemical profiling of volatile organic compounds (VOCs) emitted from microorganisms. Tetanus is a lethal disease caused by Clostridium tetani (C. tetani) bacterium and vaccination is an ultimate way to prevent this disease. In this paper, SPME fiber was used for the investigation of VOCs emerging from C. tetani during cultivation. Different types of VOCs such as sulfur-containing compounds were identified and some of them were selected as biomarkers for bioreactor monitoring during vaccine production. In the second step, the portable dynamic air sampling (PDAS) device was used as an interface for sampling VOCs by SPME fibers. The sampling procedure was optimized by face-centered central composite design (FC-CCD). The optimized sampling time and inlet gas flow rates were 10 min and 2 m L s-1, respectively. PDAS was mounted in exhausted gas line of bioreactor and 42 samples of VOCs were prepared by SPME fibers in 7 days during incubation. Simultaneously, pH and optical density (OD) were evaluated to cultivation process which showed good correlations with the identified VOCs (>80%). This method could be used for VOCs sampling from off-gas of a bioreactor to monitoring of the cultivation process.


Hyperbaric oxygen treatment mitigates liver damage in mice with noise exposure.
Noise exposure relates to various pathological disorders including liver damage, preventive measures of which are being demanded. Hyperbaric oxygen treatment (HBOT), as a non-invasive procedure, exerts convincing therapeutic potency on multiple liver diseases. The efficacy of HBOT in mitigating noise induced liver damage (NILD) and associated mechanisms would be elucidated here. Mice were subject to broad band noise (20-20k Hz, 90-110 dB) for 5 days by 3 hours/day. HBOT with 2.5 atmosphere absolute (ata) was employed before noise exposure. Morphology of liver tissue was examined by hematoxylin-eosin (HE) staining. Oil Red O (ORO), transferase-mediated dUTP nick end labelling (TUNEL) test and western blot were utilized to detect lipid accumulation, apoptotic cells and protein expression, respectively. Ceramide (Cer) level was assayed by immunohistochemistry (IHC) analysis. With noise exposure, conspicuous structural derangement and lipid deposition occurred in liver tissue of mice, which was alleviated significantly by the application of HBOT. Meanwhile, HBOT reduced the proportion of apoptotic hepatocytes, restraining the superoxide production in noise exposed mice. In view of underlying mechanisms, noise enhanced the acid sphingomyelinase (ASM) protein expression and the Cer generation in liver tissue of mice which was reversed substantially by HBOT. Altogether, HBOT ameliorates the structural and functional derangement of liver by neutralizing the ASM/Cer pathway in noise exposed mice.


Expression of flTF and asTF splice variants in various cell strains and tissues.
Tissue factor (TF) expressed at the protein level includes two isoforms: The membrane‑bound full‑length TF (flTF) and the soluble alternatively spliced TF (asTF). flTF is the major thrombogenic form of TF, whereas asTF is more closely associated with tumor growth, angiogenesis, metastasis and cell growth. In order to further investigate the different expression and functions of TF splice variants, the expression of these two splice variants were detected in numerous cell strains and tissues in the present study. Quantitative polymerase chain reaction was used to measure the transcript levels of the TF variants in 11 human cell lines, including cervical cancer, breast cancer, hepatoblastoma, colorectal cancer and umbilical vein cells, and five types of tissue specimen, including placenta, esophageal cancer, breast cancer, cervical cancer (alongside normal cervical tissues) and non‑small cell lung cancer (alongside adjacent and normal tissues). Furthermore, the effects of chenodeoxycholic acid (CDCA) and apolipoprotein M (apoM) on the two variants were investigated. The results demonstrated that flTF was the major form of TF, and the mRNA expression levels of flTF were higher than those of asTF in all specimens tested. CDCA significantly upregulated the mRNA expression levels of the two variants. Furthermore, overexpression of apoM promoted the expression levels of asTF in Caco‑2 cells. The mRNA expression levels of asTF in cervical cancer tissues were significantly higher than in the corresponding normal tissues. To the best of our knowledge, the present study is the first to compare the expression of flTF and asTF in various samples. The results demonstrated that CDCA and apoM may modulate TF isoforms in different cell lines, and suggested that asTF may serve a role in the pathophysiological mechanism underlying cervical cancer development. In conclusion, the TF isoforms serve important and distinct roles in pathophysiological processes.


Nivolumab in squamous cell carcinoma of the head and neck.
The prognosis of recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (HNSCC) after failure of first line chemotherapy is dismal. Until the publication of the results of CheckMate 141, not a single agent provided any survival benefit as a second line treatment for R/M HNSCC. Areas covered: A comprehensive review of the literature was conducted on the role of nivolumab in HNSCC. Expert commentary: Nivolumab is approved by the Food and Drug Administration for the treatment of patients based on the results of CheckMate 141 showing an overall survival benefit as compared to standard care (single agent docetaxel, methotrexate, or cetuximab). Of particular interest are immune-related adverse events which should be managed according to published guidelines.


[The effect of acetylcholine and atropine on proliferation and differentiation and mAchR1 expression of human SK-N-SH cells].
The SK-N-SH human neuroblastoma cells were treated with acetylcholine (Ach) and atropine (Atro), the proliferation activity of cells was detected by CCK-8 method and the cell cycle distribution was determined by flow cytometry. The changes of the mRNA and protein of mAchR1 and c-fos were analysed by fluorescence quantitative PCR, western blot and flow cytometry indirect-immunofluorescence. Results showed 1 mmol/L Ach could significantly stimulate the proliferation of SK-N-SH cells and 1 mmol/L Atro could prevent SK-N-SH cells from S phase growing into G2/M phase; 1 mmol/L Ach and 1 mmol/L Atro had feedback adjustment on the protein level of mAchR1, but had no significant effect on mRNA level of mAchR1. 1 mmol/L Ach increased the both levels of mRNA and protein of Fos obviously, this effect was reversed by Atro. All phenomena clue us cholinergic receptors joining the events of cell proliferation.


Paroxysmal Kinesigenic Dyskinesia as the Presenting and Only Manifestation of Multiple Sclerosis after Eighteen Months of Follow-Up.
Other than tremor, movement disorders are uncommon in multiple sclerosis. Among these uncommon clinical manifestations, paroxysmal kinesigenic dyskinesia is the most frequently reported. It is characterized by episodic attacks of involuntary movements that are induced by repetitive or sudden movements, startling noise or hyperventilation. The diagnosis is essentially clinical and based on a good observation of the attacks. It is very easy to misdiagnose it. We describe the case of a young female patient who presented paroxysmal kinesigenic dyskinesia as the first and only clinical manifestation of multiple sclerosis, with no recurrence of attacks nor any other neurologic symptom after eighteen months of follow-up.


Martial arts intervention decreases pain scores in children with malignancy.
Martial arts intervention in disease has been mostly limited to adult inflammatory, musculoskeletal, or motor diseases, where a mechanical intervention effects positive change. However, the application and benefit to pain management in childhood malignancy are not well described. Here, we assess the effects of defined martial arts intervention in children with cancer with respect to their pain perception and management. Sixty-four children with childhood malignancies were enrolled in a martial arts program, which encompassed both meditation and movement modalities. Pain scores (0-10) were recorded pre- and post- 1-hour session intervention. Pain scores were crossed by total visits and tabulated by whether participant pain reduced at least 1 unit, stayed the same, or increased in intensity immediately after (post) participation session. Differences in pain scores were further compared by age and sex. Prepain and postpain scale data were measured for 64 participants, 43 males (67.2%) and 21 females (32.8%), ranging from 3 years to 19 years. Preintervention and postintervention data were obtained for 223 individual session visits. Mean number of patient participation visits was 1.8±1.6 (range one to nine visits). Of 116 individual measured sessions where the participants began with a pain score of at least 1, pain intensity reduced ≥1 unit in 85.3% (99/116) of visits, remained the same in 7.8% (9/116), and increased in 6.9% (8/116). For the majority (96.3%; 77/80) of sessions, participants began with a prepain intensity score of at least 5-10 with reduction in pain intensity following the session. The overall mean pain score presession visit was reduced bŷ40% (pre: 5.95±2.64 and post: 3.03±2.45 [95% CI: 2.34-3.50]; P≤0.001). Median pain intensity scores had greater reductions with increased age of participants (3-6 years [-1], 7-10 years [-2], 11-14 years [-3], and 15-19 years [-4]). Martial arts intervention can provide a useful modality to decrease pain in childhood cancer, with greater effect achieved with higher baseline pain scores and patient age. Martial arts intervention may improve patient compliance with respect to medical and surgical management, thus reducing disease morbidity and health care costs.


Effect of temperature on isolated stretch-receptor organ of the crayfish.
Abdominal stretch-receptor organs of Astacus leptodactylus are investigated by means of extra- and intracellular leads. The effects of changing temperature on steady-state rate of activity are surprisingly low. The sensory nerve cell compensates for changes in temperature by means of opposite reactions of generator potential and threshold.


The N terminus of the anti-apoptotic BCL-2 homologue MCL-1 regulates its localization and function.
The BCL-2 homologue MCL-1 plays an important role in the regulation of cell fate by blocking apoptosis as well as regulating cell cycle. MCL-1 has an unusual N-terminal extension, which contains a PEST domain and several phosphorylation sites that have been suggested to regulate its turnover. Here we report that the first 79 amino acids of MCL-1 regulate its subcellular localization. Deletion of this domain impairs both its mitochondrial localization and its anti-apoptotic activity. Conversely, expression of the N terminus of MCL-1 promotes both the association of MCL-1 with mitochondria and cell survival in a fashion that is dependent on the presence of endogenous MCL-1. In addition, the N terminus of MCL-1 has an antagonistic effect on proliferation. Although MCL-1 decreases proliferation through binding to proliferating cell nuclear antigen and cyclin-dependent kinase 1 in the nucleus, the N terminus of MCL-1 accelerates cell division. On the other hand, deletion of this region further increases the anti-proliferative activity of MCL-1. These results suggest that the N terminus of MCL-1 plays a major regulatory role, regulating coordinately the mitochondrial (anti-apoptotic) and nuclear (anti-proliferative) functions of MCL-1.


Update on time-of-flight PET imaging.
Time-of-flight (TOF) PET was initially introduced in the early days of PET. The TOF PET scanners developed in the 1980s had limited sensitivity and spatial resolution, were operated in 2-dimensional mode with septa, and used analytic image reconstruction methods. The current generation of TOF PET scanners has the highest sensitivity and spatial resolution ever achieved in commercial whole-body PET, is operated in fully-3-dimensional mode, and uses iterative reconstruction with full system modeling. Previously, it was shown that TOF provides a gain in image signal-to-noise ratio that is proportional to the square root of the object size divided by the system timing resolution. With oncologic studies being the primary application of PET, more recent work has shown that in modern TOF PET scanners there is an improved tradeoff between lesion contrast, image noise, and total imaging time, leading to a combination of improved lesion detectability, reduced scan time or injected dose, and more accurate and precise lesion uptake measurement. Because the benefit of TOF PET is also higher for heavier patients, clinical performance is more uniform over all patient sizes.


A confirmatory factor analytic approach on perceptions of knowledge and skills in teaching (PKST).
This paper reports the cross-validation of the factor pattern of the Perceptions of Knowledge and Skills in Teaching (PKST) survey, which was used to assess the self-perceived pedagogical knowledge and skills of pre-service and beginning teachers. The sample comprised 323 pre-service teachers enrolled in a 1-yr. post-graduate teacher education program in Singapore. The survey had 37 items distributed across six scales: student learning, lesson planning, instructional support, accommodating diversity, classroom management, and care and concern. A confirmatory factor analysis (CFA) was used to cross-validate the survey's factor pattern. The results showed that the model was an acceptable fit to the data. The PKST survey can thus be adapted by different teacher education programs to assess pre-service and beginning teachers' progress in developing their pedagogical knowledge and skills.


Smoking cessation in women with cardiac risk.
This article summarizes what is known about smoking among women, in particular the consequences of smoking on women's cardiac health. Smoking is recognized as a major independent cause of coronary heart disease, a condition that ranks first among the causes of death for middle-aged and older women. Women who stop smoking greatly reduce their risk of heart disease and other smoking-related illnesses. Research since the 1980 report of the US Surgeon General has been inconsistent in finding differences by gender in smoking cessation, and few approaches have been devised specifically for women. Several factors are of unique concern among women and potential barriers to smoking cessation, including weight concerns, negative affect regulation, and hormonal influences. More research is needed to determine whether these factors, when targeted specifically, improve cessation success rates among women.


Anorexia nervosa in adolescents.
Anorexia nervosa is an eating disorder with peak onset in adolescence, which carries the highest mortality rate of all psychiatric illnesses. It is commonly comorbid with other physical and mental health problems, yet training on management of people with eating disorders and working knowledge of clinicians working with underweight adolescents is inconsistent. This review of anorexia nervosa in adolescents provides an overview of the presentation, aetiology and treatment of this disorder, with a particular focus on the assessment and management of physical health risks, including refeeding syndrome.


Construct validity of the self-assessment evaluation form for the Olympic Education Training Program in Greece.
The Professional Development Evaluation Form, developed to evaluate training of physical education teachers for the Olympic education program in Greece, was administered to 438 physical educators (205 men and 233 women; M age=32.2 yr., SD= 9.1). A confirmatory factor analysis indicated an adequate fit of the proposed model.


Best Practice for After-Hours Hospice Symptom Management: A Literature Review.
Medicare-certified hospice home care agencies must provide a 24/7 on-call system to respond to patient and caregiver concerns. How these calls are handled impacts patient and family outcomes and satisfaction. Ideally, hospice nurses provide adequate caregiver education during routine visits to minimize the need for after-hours calls. A literature review provided evidence that hospice nurse education and appropriate telephone support improves symptom management, enhances family support, provides a sense of security, reduces anxiety, and promotes comfort.


Gastric carcinoma of the umbilicus: case report of Sister Mary Joseph nodule.
Sister Mary Joseph nodule is a metastatic lesion of the umbilicus, which is an uncommon phenomenon that carries an ominous prognosis. We describe a patient with gastric cancer who presented with asymptomatic papules on the umbilicus proven to be metastatic foci by biopsy. The lesion represented spread of the malignancy despite chemotherapy; thus, treatment was initiated with second-line agents. Sister Mary Joseph nodule can be the first presenting sign of an occult malignancy, or as demonstrated in this case, a sign of disease progression. Given the variable appearance of the lesions, a high index of suspicion is necessary to make an accurate diagnosis.


Accurate frozen core approximation for all-electron density-functional theory.
We implement and benchmark the frozen core approximation, a technique commonly adopted in electronic structure theory to reduce the computational cost by means of mathematically fixing the chemically inactive core electron states. The accuracy and efficiency of this approach are well controlled by a single parameter, the number of frozen orbitals. Explicit corrections for the frozen core orbitals and the unfrozen valence orbitals are introduced, safeguarding against seemingly minor numerical deviations from the assumed orthonormality conditions of the basis functions. A speedup of over twofold can be achieved for the diagonalization step in all-electron density-functional theory simulations containing heavy elements, without any accuracy degradation in terms of the electron density, total energy, and atomic forces. This is demonstrated in a benchmark study covering 103 materials across the Periodic Table and a large-scale simulation of CsPbBr3 with 2560 atoms. Our study provides a rigorous benchmark of the precision of the frozen core approximation (sub-meV per atom for frozen core orbitals below -200 eV) for a wide range of test cases and for chemical elements ranging from Li to Po. The algorithms discussed here are implemented in the open-source Electronic Structure Infrastructure software package.


Purification of recombinant Shiga-like toxin type I A1 fragment from Escherichia coli.
Shiga-like toxin I A1 (Slt-IA1) is a RNA N-glycosidase which depurinates a specific adenosine of 28 S eukaryotic rRNA thus inhibiting protein synthesis and ultimately leading to cell death. We have overexpressed this protein in Escherichia coli using a high copy number plasmid and purified the enzyme to homogeneity using a three-step process. Slt-IA1 is released from the periplasm of cells using polymyxin B sulfate, precipitated with ammonium sulfate, and adsorbed to a Matrex Gel Green A dye-ligand agarose column. The enzyme is eluted from the Green A agarose as a single peak with 0.32 M NaCl. Slt-IA1 was purified approximately 1979-fold and routinely gave yields greater than 100%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a single band with an apparent molecular weight of 28,000. An isoelectric point of 5.1 was determined using analytical isoelectric focusing gels. In an in vitro protein synthesis inhibition assay, 0.02 pM of purified Slt-IA1 inhibited protein synthesis by 50%.


Male Cope's gray treefrogs (Hyla chrysoscelis) in amplexus have elevated and correlated steroid hormones compared to solitary males.
Gonadal steroid hormones are typically elevated during the breeding season-a finding known as an associated reproductive pattern. Though less studied, there is also evidence, in both sexes, for elevated adrenal/interrenal steroids, including acute elevations on the day of mating. I investigated gonadal and interrenal steroids in wild male Cope's gray treefrogs at breeding aggregations. I collected blood from males found in amplexus with female mates (amplexed males) and males sampled at the same time and location that were actively advertising vocally and without a mate (solo males). Concentrations of plasma corticosterone, testosterone, and 17β-estradiol (CORT, T and E2, respectively) were validated and measured. These two categories of males differed in four ways: (1) amplexed males exhibited significantly elevated concentrations of all three steroids compared to solo males (CORT: +347 %; T: +60 %; and E2: +43 %); (2) these hormone profiles alone accurately predicted male mating category with ca. 83 % accuracy using a discriminant function analysis; (3) amplexed males exhibited significant between-hormone correlations (T and E2 were positively correlated and CORT and E2 were negatively correlated) whereas no correlations were found in solo males; (4) amplexed males showed a negative correlation with CORT concentration and the time of night, whereas no such pattern was present in solo males. These findings suggest an acute and strong coactivation of the interrenal and gonadal axes that could drive phenotypic integration during this fitness-determining moment. I discuss these findings and suggest experiments to determine causation, including the role of motor behavior driving endocrine states and the role of female selection on endocrine profiles.


Effect of the driving frequency on the emission characteristics of a radio-frequency glow discharge excitation source boosted by the introduction of a d. c. bias current.
In a radio-frequency-powered glow discharge lamp, a d.c. bias current which is driven by a self-bias voltage can lead to an enhancement of the emission intensities excited by the plasma. The driving frequency of the r.f. plasma is an important parameter to determine the self-bias voltage; lower r.f. frequencies induce greater self-bias voltages. The effects of the bias current introduction on the emission characteristics were compared between a 13.56-MHz plasma and a 6.78-MHz plasma. As a result, the 6.78-MHz plasma offered a better analytical performance, probably due to higher self-bias voltages, if the introduced Ar pressure was optimized. This method was applied to a Mo determination in Fe-matrix alloy samples. At bias currents of 40 - 50 mA, the emission intensities of the Mo I 379.82-nm line were about 10-times larger than those obtained with the conventional plasma when the 6.78-MHz plasma was produced at an r.f. power of 60 W. The detection limit obtained for this calibration was 2.0 x 10(-4) mass % Mo at an 80-W r.f. power and at a d.c. bias current of 68 mA.


Did pollination shifts drive diversification in southern African Gladiolus? Evaluating the model of pollinator-driven speciation.
The pollinator-driven ecological speciation model has frequently been invoked to explain plant richness in biodiversity hotspots. Here, by focusing on Gladiolus (260 species), a flagship example of a clade with diverse pollination biology, we test the hypothesis that high species diversity in southern Africa, one of the world's most floristically rich regions, has primarily been driven by ecological shifts in pollination systems. We use phylogenetic methods to estimate rates of transition between the seven highly specialized pollination strategies in Gladiolus. We find that pollination systems have evolved multiple times and that some pollination strategies arose by a variety of evolutionary pathways. Pollination shifts account for up to one-third of all lineage splitting events in the genus, providing partial support for the pollinator-driven speciation model. Transitions from the ancestral pollination mode to derived systems have also resulted in increased rates of diversification, suggesting that certain pollination systems may speed up speciation processes, independently of pollination shifts per se. This study suggests that frequent pollination shifts have played a role in driving high phenotypic and species diversity but indicates that additional factors need to be invoked to account for the spectacular diversification in southern African Gladiolus.


Activation of cartilage-derived morphogenetic protein-1 in torn rotator cuff.
Localization and expression of cartilage-derived morphogenetic protein-1 in tissues of torn rotator cuff tendons were examined by in situ hybridization and immunohistochemical analysis. Histologic findings of torn rotator cuff tendons showed that active cells synthesizing the alpha-1 chain of collagen Type I messenger ribonucleic acid were localized predominantly in the torn edge and in the bursa side rather than in the joint side, and scarcely localized in a site distant from the torn edge. Cartilage-derived morphogenetic protein-1 had a similar distribution as the alpha-1 chain of collagen Type I. The current findings provide the first observational evidence that cartilage-derived morphogenetic protein-1 was activated specifically at the site of the torn rotator cuff tendon. The current findings suggest that the cells in the torn rotator cuffs are capable of synthesizing cartilage-derived morphogenetic protein-1, one of the known essential factors for tendon formation.


Determination of Hg, Fe, Ni, and Co by Miniaturized Optical Emission Spectrometry Integrated with Flow Injection Photochemical Vapor Generation and Point Discharge.
A compact and robust OES technique was developed for the sensitive determination of Hg, Fe, Ni, and Co by utilizing photochemical vapor generation and point discharge as the sampling technique and the excitation source, respectively. Mercury cold vapor and the volatile species of Fe, Ni, and Co were generated when standard or sample solutions containing formic acid were exposed to a UV photochemical reactor and subsequently separated from the liquid phase for transport to the microplasma and detection of their atomic emission. Limits of detection (LODs) of 0.10, 10, 0.20, and 4.5 μg L(-1) were obtained for Hg, Fe, Ni and Co, respectively. Compared to conventional microplasma OES, this method not only broadens the scope of elements amenable to determination, but also provides 2- and 7-fold improvement in the LODs for Hg and Ni, respectively. Method validation was demonstrated by analysis of three Certified Reference Materials (GBW08607, DORM-3, and DORM-4) with satisfactory results, and by good spike recoveries (93-111%) from three real water samples.


Molecular epidemiology and antimicrobial susceptibility of diarrheagenic Escherichia coli isolated from children under age five with and without diarrhea in Central Ethiopia.
Diarrhea is a serious health problem in children, with the highest mortality rate in sub-Saharan Africa. Diarrheagenic Escherichia coli (DEC) is among the major bacterial causes of diarrhea in children under age five. The present study aims to determine molecular epidemiology and antimicrobial resistance profiles of DEC and identify contributing factors for acquisition among children under age five in Central Ethiopia. A health facility-centered cross-sectional study was conducted in Addis Ababa and Debre Berhan, Ethiopia, from December 2020 to August 2021. A total of 476 specimens, 391 from diarrheic and 85 from non-diarrheic children under age five were collected. Bacterial isolation and identification, antimicrobial susceptibility, and pathotype determination using polymerase chain reaction (PCR) were done. Of the 476 specimens analyzed, 89.9% (428/476) were positive for E. coli, of which 183 were positive for one or more genes coding DEC pathotypes. The overall prevalence of the DEC pathotype was 38.2% (183/476). The predominant DEC pathotype was enteroaggregative E. coli (EAEC) (41.5%, 76/183), followed by enterotoxigenic E. coli (21.3%, 39/183), enteropathogenic E. coli (15.3%, 28/183), enteroinvasive E. coli (12.6%, 23/183), hybrid strains (7.1%, 13/183), Shiga toxin-producing E. coli (1.6%, 3/183), and diffusely-adherent E. coli (0.6%, 1/183). DEC was detected in 40.7% (159/391) of diarrheic and 28.2% (24/85) in non-diarrheic children (p = 0.020). The majority of the DEC pathotypes were resistant to ampicillin (95.1%, 174/183) and tetracycline (91.3%, 167/183). A higher rate of resistance to trimethoprim-sulfamethoxazole (58%, 44/76), ciprofloxacin (22%, 17/76), ceftazidime and cefotaxime (20%, 15/76) was seen among EAEC pathotypes. Multidrug resistance (MDR) was detected in 43.2% (79/183) of the pathotypes, whereas extended spectrum ß-lactamase and carbapenemase producers were 16.4% (30/183) and 2.2% (4/183), respectively. All six common DEC pathotypes that have the potential to cause severe diarrheal outbreaks were found in children in the study area; the dominant one being EAEC with a high rate of MDR.


Neutron and X-ray effects on small intestine summarized by using a mathematical model or paradigm.
The responses of intestinal tissues to ionizing radiation can be described by comparing irradiated cell populations qualitatively or quantitatively with corresponding controls. This paper describes quantitative data obtained from resin-embedded sections of neutron-irradiated mouse small intestine at different times after treatment. Information is collected by counting cells or structures present per complete circumference. The data are assessed by using standard statistical tests, which show that early mitotic arrest precedes changes in goblet, absorptive, endocrine and stromal cells and a decrease in crypt numbers. The data can also produce ratios of irradiated: control figures for cells or structural elements. These ratios, along with tissue area measurements, can be used to summarize the structural damage as a composite graph and table, including a total figure, known as the Morphological Index. This is used to quantify the temporal response of the wall as a whole and to compare the effects of different qualities of radiation, here X-ray and cyclotron-produced neutron radiations. It is possible that such analysis can be used predictively along with other reference data to identify the treatment, dose and time required to produce observed tissue damage.


Computed tomography after partial hepatectomy.
Twenty-two patients with surgically resectable malignant primary liver neoplasm or hepatic metastases were examined by computed tomography both before and after surgery. The anatomic modifications created by the surgery, including right lobectomy, left lobectomy, segmentectomy, and wedge resections were evaluated. Computed tomography depicted changes in the liver contour, usually after right or left lobectomy as well as secondary effects of these changes in the adjacent organs. With knowledge of these postsurgical modifications, the reparative ability of the liver can be appreciated.